In this issue, Pingze Zhang et al. reveal that S6K suppression in the fruit-fly fat body mediates the longevity effects of rapamycin, and uncover a sex-dimorphic link through to lysosome morphology and inflammation, via Syntaxin 13. The cover image conceptualizes the link to inflammaging by depicting aged flies as confined to a jar (representing the nuclear localization of the Drosophila NFκB-like transcription factor Relish), emitting brighter light (representing upregulation of inflammatory mediators).

See Zhang et al.

In this issue, Kojiro Suda, Yohsuke Moriyama, Nurhanani Razali and colleagues set out, using a genome-wide screen and gene-expression analysis in budding yeast, to better understand the cellular response to plasma membrane damage. The team discover that damage to the plasma membrane can limit replicative lifespan in yeast and induce senescence in human fibroblasts. The cover image shows kintsugi, the traditional Japanese art of repairing broken pottery by mending the cracks with urushi and gold. Kintsugi visibly incorporates the history of an object into its new form and thus transforms it. In this analogy, cell membrane damaged is repaired; however, rather than restoring the cell to its previous form, the new cellular nature is irreversibly changed and distinct from its previous state.

See Suda et al.

In this issue, Kejun Ying et al. identify CpGs that may be causally linked to aging-related traits using epigenome-wide Mendelian randomization. They develop the epigenetic clocks DamAge and AdaptAge, which track adverse and adaptive outcomes, respectively. The cover image conceptualizes the relationship between DNA methylation and the aging process as a cascade of dominoes that links the youthful individual with the old one. Each domino represents a key CpG site with a causal influence on aging undergoing methylation (denoted by the letter ‘M’). The falling of the dominoes embodies causal effects of these methylation events, suggesting a sequential impact on the progression of aging.

See Ying et al.

In this issue, Netta Mendelson Cohen et al. investigate individuals’ trajectories of healthy aging and age-related diseases. The researchers stitch together electronic health records with partial longitudinal coverage, using machine learning to untangle future healthy aging from chronic disease, and identify early indicators for healthy longevity. The cover image shows the study’s longevity-model features superimposed with representations of electronic health record information, which are connected via multiple solid or dotted lines that indicate differing propensities to drive the outputs of the models.

See Cohen et al.